chr19-54276833-C-T

Variant names:

• chr19-54276833-C-T
• rs111762694
• NM_001080978.4:c.1454G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080978.4(LILRB2):​c.1454G>A​(p.Arg485Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: LILRB2 NM_001080978.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.63
• Publications: 0 publications found

Genes affected

LILRB2 (HGNC:6606): (leukocyte immunoglobulin like receptor B2) This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014740795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080978.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	NM_001080978.4	MANE Select	c.1454G>A	p.Arg485Gln	missense	Exon 10 of 14	NP_001074447.2	Q8N423-2
	LILRB2	NM_005874.5		c.1457G>A	p.Arg486Gln	missense	Exon 10 of 14	NP_005865.3	Q8N423-1
	LILRB2	NM_001278403.3		c.1454G>A	p.Arg485Gln	missense	Exon 10 of 14	NP_001265332.2	Q8N423-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB2	ENST00000314446.10	TSL:1 MANE Select	c.1454G>A	p.Arg485Gln	missense	Exon 10 of 14	ENSP00000319960.5	Q8N423-2
	LILRB2	ENST00000391749.4	TSL:1	c.1457G>A	p.Arg486Gln	missense	Exon 10 of 14	ENSP00000375629.4	Q8N423-1
	LILRB2	ENST00000391748.5	TSL:1	c.1454G>A	p.Arg485Gln	missense	Exon 10 of 14	ENSP00000375628.1	Q8N423-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152000 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000522 AC: 13 AN: 248880 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000224 AC: 10 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111934

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152000 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74232

African (AFR) AF: 0.0000483 AC: 2 AN: 41384

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.15
DANN	Benign	0.82
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.00086	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.91	T
PhyloP100		-3.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.025
Sift	Benign	0.26	T
Sift4G	Benign	0.23	T
Vest4		0.11
MVP		0.076
MPC		0.051
ClinPred		0.043	T
GERP RS		-3.0
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs111762694; hg19: chr19-54780687;